Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice
Introduction: Vestibular sensory hair cells are precisely orientated according to planar cell polarity (PCP) and are key to enable mechanic-electrical transduction and normal vestibular function. PCP is found on different scales in the vestibular organs, ranging from correct hair bundle orientation,...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.750596/full |
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| author | François Simon François Simon Fadel Tissir Fadel Tissir Vincent Michel Ghizlene Lahlou Ghizlene Lahlou Michael Deans Michael Deans Mathieu Beraneck |
| author_facet | François Simon François Simon Fadel Tissir Fadel Tissir Vincent Michel Ghizlene Lahlou Ghizlene Lahlou Michael Deans Michael Deans Mathieu Beraneck |
| author_sort | François Simon |
| collection | DOAJ |
| description | Introduction: Vestibular sensory hair cells are precisely orientated according to planar cell polarity (PCP) and are key to enable mechanic-electrical transduction and normal vestibular function. PCP is found on different scales in the vestibular organs, ranging from correct hair bundle orientation, coordination of hair cell orientation with neighboring hair cells, and orientation around the striola in otolithic organs. Celsr1 is a PCP protein and a Celsr1 KO mouse model showed hair cell disorganization in all vestibular organs, especially in the canalar ampullae. The objective of this work was to assess to what extent the different vestibulo-ocular reflexes were impaired in Celsr1 KO mice.Methods: Vestibular function was analyzed using non-invasive video-oculography. Semicircular canal function was assessed during sinusoidal rotation and during angular velocity steps. Otolithic function (mainly utricular) was assessed during off-vertical axis rotation (OVAR) and during static and dynamic head tilts.Results: The vestibulo-ocular reflex of 10 Celsr1 KO and 10 control littermates was analyzed. All KO mice presented with spontaneous nystagmus or gaze instability in dark. Canalar function was reduced almost by half in KO mice. Compared to control mice, KO mice had reduced angular VOR gain in all tested frequencies (0.2–1.5 Hz), and abnormal phase at 0.2 and 0.5 Hz. Concerning horizontal steps, KO mice had reduced responses. Otolithic function was reduced by about a third in KO mice. Static ocular-counter roll gain and OVAR bias were both significantly reduced. These results demonstrate that canal- and otolith-dependent vestibulo-ocular reflexes are impaired in KO mice.Conclusion: The major ampullar disorganization led to an important reduction but not to a complete loss of angular coding capacities. Mildly disorganized otolithic hair cells were associated with a significant loss of otolith-dependent function. These results suggest that the highly organized polarization of otolithic hair cells is a critical factor for the accurate encoding of the head movement and that the loss of a small fraction of the otolithic hair cells in pathological conditions is likely to have major functional consequences. Altogether, these results shed light on how partial loss of vestibular information encoding, as often encountered in pathological situations, translates into functional deficits. |
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| spelling | doaj.art-acd7d011ef694444b4d8a385852e4f822022-12-21T22:35:18ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-11-011510.3389/fnins.2021.750596750596Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– MiceFrançois Simon0François Simon1Fadel Tissir2Fadel Tissir3Vincent Michel4Ghizlene Lahlou5Ghizlene Lahlou6Michael Deans7Michael Deans8Mathieu Beraneck9Université de Paris, INCC UMR 8002, CNRS, Paris, FranceService d’ORL et de Chirurgie Cervico-Faciale Pédiatrique, AP-HP, Hôpital Necker-Enfants Malades, Paris, FranceInstitut de Neuroscience, Université Catholique de Louvain, Brussels, BelgiumCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarInstitut de l’Audition, Institut Pasteur, INSERM, Paris, FranceInstitut de l’Audition/Institut Pasteur, Technologies et thérapie génique pour la surdité, Paris, FranceService d’ORL et de Chirurgie Cervico-Faciale Pédiatrique, APHP, Sorbonne Université, Hôpital Pitié-Salpétrière, Paris, FranceDepartment of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT, United StatesDivision of Otolaryngology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, United StatesUniversité de Paris, INCC UMR 8002, CNRS, Paris, FranceIntroduction: Vestibular sensory hair cells are precisely orientated according to planar cell polarity (PCP) and are key to enable mechanic-electrical transduction and normal vestibular function. PCP is found on different scales in the vestibular organs, ranging from correct hair bundle orientation, coordination of hair cell orientation with neighboring hair cells, and orientation around the striola in otolithic organs. Celsr1 is a PCP protein and a Celsr1 KO mouse model showed hair cell disorganization in all vestibular organs, especially in the canalar ampullae. The objective of this work was to assess to what extent the different vestibulo-ocular reflexes were impaired in Celsr1 KO mice.Methods: Vestibular function was analyzed using non-invasive video-oculography. Semicircular canal function was assessed during sinusoidal rotation and during angular velocity steps. Otolithic function (mainly utricular) was assessed during off-vertical axis rotation (OVAR) and during static and dynamic head tilts.Results: The vestibulo-ocular reflex of 10 Celsr1 KO and 10 control littermates was analyzed. All KO mice presented with spontaneous nystagmus or gaze instability in dark. Canalar function was reduced almost by half in KO mice. Compared to control mice, KO mice had reduced angular VOR gain in all tested frequencies (0.2–1.5 Hz), and abnormal phase at 0.2 and 0.5 Hz. Concerning horizontal steps, KO mice had reduced responses. Otolithic function was reduced by about a third in KO mice. Static ocular-counter roll gain and OVAR bias were both significantly reduced. These results demonstrate that canal- and otolith-dependent vestibulo-ocular reflexes are impaired in KO mice.Conclusion: The major ampullar disorganization led to an important reduction but not to a complete loss of angular coding capacities. Mildly disorganized otolithic hair cells were associated with a significant loss of otolith-dependent function. These results suggest that the highly organized polarization of otolithic hair cells is a critical factor for the accurate encoding of the head movement and that the loss of a small fraction of the otolithic hair cells in pathological conditions is likely to have major functional consequences. Altogether, these results shed light on how partial loss of vestibular information encoding, as often encountered in pathological situations, translates into functional deficits.https://www.frontiersin.org/articles/10.3389/fnins.2021.750596/fullvestibulo ocular reflexplanar cell polarity (PCP)vestibular systemCELSR1mouse modelhair cell |
| spellingShingle | François Simon François Simon Fadel Tissir Fadel Tissir Vincent Michel Ghizlene Lahlou Ghizlene Lahlou Michael Deans Michael Deans Mathieu Beraneck Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice Frontiers in Neuroscience vestibulo ocular reflex planar cell polarity (PCP) vestibular system CELSR1 mouse model hair cell |
| title | Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice |
| title_full | Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice |
| title_fullStr | Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice |
| title_full_unstemmed | Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice |
| title_short | Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice |
| title_sort | implication of vestibular hair cell loss of planar polarity for the canal and otolith dependent vestibulo ocular reflexes in celsr1 mice |
| topic | vestibulo ocular reflex planar cell polarity (PCP) vestibular system CELSR1 mouse model hair cell |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.750596/full |
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